Studies are in progress involving the adenosine receptor using the agonist [3H] cyclohexyl-adenosine and the antagonist [3H] diphenylxanthine. It has been shown that agonist and antagonist bind to either two distinct subtypes or conformations of the receptor, since the binding of these two ligands is differentially affected by several different treatments. Chronic caffeine treatment has been shown to cause a marked increase in the number of adenosine receptors in brain. The adenosine uptake inhibitor [3H] nitrobenzylthioinosine has been shown to be a photoaffinity probe for the adenosine uptake site with short exposures to ultraviolet light causing an apparently irreversible interaction. The sedative effects of adenosine have been shown to be potentiated by pretreatment of mice with nitrobenzylthioinosine. The relationship of adenosine receptors with calcium channels has prompted us to continue our study of the binding of the calcium antagonist, [3H] nitrendipine to brain membranes. The ontogeny of [3H] nitrendipine binding sites in chick brain and heart is being studied in an attempt to correlate the binding site to defined physiological processes. The study of 14C 2-deoxyglucose uptake in brain and its regional modulation by adenosine agonists and antagonists is also under study in an effort to identify functional adenosine receptors.